Distinct clustering of point mutations in mitochondrial DNA among patients with mitochondrial encephalomyopathies and with Parkinson's disease

Ozawa, Takayuki; Tanaka, Masashi; Ino, Hidekazu; Ohno, Kinji; Sano, Takuya; Wada, Yoshiro; Yoneda, Makoto; Tanno, Y; Miyatake, Tadashi; Tanaka, Taihei; Itoyama, Shinji; Ikebe, Shin-ichiro; Hattori, Nobutaka; Mizuno, Yoshikuni

doi:10.1016/s0006-291x(05)80276-1

Cited by 113 publications

(42 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All 9 patients had 2 polymorphisms that are probably more common in the human population than are the corresponding "Cambridge" assignments: the first was an A -. G at position 750, and the second an A -> G at position 1438 (both alterations have been noted previously (33,34). We also detected small insertions and deletions in noncoding regions, most of which were also present in normal individuals and were therefore considered neutral variants.…”

Section: Resultssupporting

confidence: 79%

Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot?

et al. 1993

View full text Add to dashboard Cite

We identified two patients with pathogenic single nucleotide changes in two different mitochondrial tRNA genes: the first mutation in the tRNAAsn gene, and the ninth known mutation in the tRNAI11(UI) gene. The mutation in tRNA " was associated with isolated ophthalmoplegia, whereas the mutation in tRNA-e(uuR) caused a neurological syndrome resembling MERRF (myoclonus epilepsy and ragged-red fibers) plus optic neuropathy, retinopathy, and diabetes. Both mutations were heteroplasmic, with higher percentages of mutant mtDNA in affected tissues, and undetectable levels in maternal relatives. Analysis of single muscle fibers indicated that morphological and biochemical alterations appeared only when the proportions of mutant mtDNA exceeded 90% of the total cellular mtDNA pool. The high incidence of mutations in the tRNA IA(Uu]?) gene suggests that this region is an "etiologic hot spot" in mitochondrial disease. (J. Clin. Invest. 1993. 92:2906-2915

show abstract

Section: Resultssupporting

confidence: 79%

Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot?

et al. 1993

View full text Add to dashboard Cite

show abstract

“…In the present study, we established a cell model of PD using MPP + treatment, according to previous descriptions [27] . Using this model, we confirm that oxidative damage and cell death are both present in PD conditions, as indicated by accumulation of 8-oxodG + signal, a biomarker of oxidative DNA damage [7][8][9][10] , and reduction of cell viability. Consistent with our previous studies [27,28] , MPP + /MPTP could induce oxidative DNA damage in the cytoplasma at early stage, which was then translocated into the nuclei.…”

Section: Discussionsupporting

confidence: 53%

“…Although the primary cause of PD remains unclear, there has been increasing evidence suggesting the involvement of oxidative stress in PD pathogenesis [2][3][4][5][6] . The postmortem studies demonstrate that 8-hydroxy-2'-deoxyguanosine (8-oxodG), a biomarker of oxidative DNA damage, accumulates in substantia nigra neurons [7][8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

1-Methyl-4-phenyl-pyridinium time-dependently alters expressions of oxoguanine glycosylase 1 and xeroderma pigmentosum group F protein in PC12 cells

Yang

Sun

2010

Neurosci. Bull.

View full text Add to dashboard Cite

Objective To determine if DNA excision repair enzymes oxoguanine glycosylase 1 (OGG1) and xeroderma pigmentosum group F protein (XPF) are involved in the pathogenesis of Parkinson's disease (PD) in a cell model. Methods PC12 cells were treated with 1-Methyl-4-phenylpyridine ion (MPP + ) for various periods of time to induce oxidative DNA damage. MTT assay was used to determine cell viability. Immunocytochemistry with antibody against 8-hydroxy-2'-deoxyguanosine (8-oxodG) was used to evaluate oxidative DNA damage. Immunoblotting was used to detect the protein levels of OGG1 and XPF. Results MPP + treatment (1 mmol/L) for 18 h and 24 h reduced cell viability to 78.6% and 70.3% of the control, respectively, in a time-dependent way. MPP + increased the immunoreactivity of 8-oxodG in the cytoplasm at 3 h and in the nucleus at 24 h of treatment. With the treatment of MPP + , the expression of OGG1 was significantly increased at 1 h, reaching a peak at 3 h, and then it was decreased at 24 h, as compared to that with vehicle treatment. The same effect was exerted on XPF level, except that the XPF level reached a peak at 18 h of MPP + treatment. Moreover, the maximally-increased protein level of OGG1 by MPP + was approximately 2-fold higher than that of XPF. Conclusion MPP + treatment could timedependently induce increases in OGG1 and XPF expressions in PC12 cells. Also, this study indicates that the base and nucleotide excision repair pathways may be compensatorily activated in the early stage of pathogenesis in the cells after MPP + treatment.

show abstract

“…Stepping beyond Genography, control mutations assigned to N9a have also been checked in connection with diseases such as mitochondrial encephalomyopathies 47 and Parkinson's disease. In connection with the latter, the C16257A and C16261T were mentioned.…”

Section: Discussionmentioning

confidence: 99%

HVS-I polymorphism screening of ancient human mitochondrial DNA provides evidence for N9a discontinuity and East Asian haplogroups in the Neolithic Hungary

et al. 2011

View full text Add to dashboard Cite

Analysis of mitochondrial mutations in the HVS-I region is an effective method for ancient human populational studies. Discontinuous haplotype data between the first farmers and contemporary Europeans has been described before. Our contribution is based on a survey initiated on the Neolithic skeletons from Hungarian archaeological sites in the Alfö ld. This Lowland, the Hungarian Plain, is well excavated as an important region for spread of Neolithic culture from Near East and Balkans toward Central and Western Europe, started circa 8000 years ago. HVS-I sequences from nt15977 to nt16430 of 11 such specimens with sufficient mitochondrial DNA preservation among an extended Neolithic collection were analysed for polymorphisms, identifying 23 different ones. After assigning all single-nucleotide polymorphisms, a novel, N9a, N1a, C5, D1/G1a, M/R24 haplogroups were determined. On mitochondrial control mutations at nt16257 and nt16261, polymorphic PCRs were carried out to assess their distribution in remains. Neolithic data set was compared with contemporary Vá c samples and references, resulting in higher frequency of N9a in Alfö ld as a remarkable genetic discontinuity. Our investigation is the first to study mutations form Neolithic of Hungary, resulting in an outcome of Far Eastern haplogroups in the Carpathian Basin. It is worth further investigation as a non-descendant theory, instead of a continuous population history, supporting genetic gaps between ancient and recent human populations.

show abstract

Distinct clustering of point mutations in mitochondrial DNA among patients with mitochondrial encephalomyopathies and with Parkinson's disease

Cited by 113 publications

References 24 publications

Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot?

Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot?

1-Methyl-4-phenyl-pyridinium time-dependently alters expressions of oxoguanine glycosylase 1 and xeroderma pigmentosum group F protein in PC12 cells

HVS-I polymorphism screening of ancient human mitochondrial DNA provides evidence for N9a discontinuity and East Asian haplogroups in the Neolithic Hungary

Contact Info

Product

Resources

About